1. We have demonstrated previously that the deoxyglucose (DG) transport rate was lower than the methylglucose (MG) transport rate and that the DG can be accelerated up to the MG transport rate. Last year we demonstrated in plasma membrane vesicles (PMV) that the DG transport rate was equivalent to the MG rate, and the two sugars had similar kinetics. This suggests that the lower DG transport rate seen previously in adipocytes was dependent upon intracellular substrates, enzymes and/or organelles for its expression. Glucose-6-phosphate (G6P) decreased both MG and glucose, but not DG transport in adipocytes. In contrast MD, DG, and glucose transport rates were all inhibited by G6P in PMV. This year we have determined that the effect of G6P on sugar transport was time and concentration dependent in both adipocytes and PMV. Furthermore, G6P was taken into the intracellular and intravesicular spaces. The G6P effect was not mimicked by the sugar phosphates. G6P decreases Vmax and Ks in both O-trons and equilibrium exchange MG experiments suggesting that the effect of G6P is not via competitive inhibition, nor via a change in the symmetry of the transport system. Their data indicates that G6P can negatively regulate sugar transport in rat adipocytes. Furthermore G6P is not the accelerating factor of DG transport in adipocytes which was produced in cells during incubation with glucose. The data provides direct evidence that sugar transport can be modulated by changes in intracellular metabolites. 2. We have demonstrated that MG transport in both rat and human adipocytes are regulated by 3 different mechanisms. I. Isoproterenol, a B-agonist, stimulated MG transport by increasing Vmax, but not beyond the maximum insulin stimulated rate. II. CAMP mediates a decrease in MG transport by decreasing Vmax. III. Both forskolin, a direct stimulator of adenylate cyclase, and IBMx, a phosphodiesterase inhibitor, independent of their effects on CAMP levels decrease MG transport by directly inhibiting the binding of MG molecules to transports, resulting in a decrease in the Vmax and an increase in the KS. The relative effectiveness among the 3 mechanisms is different between rat and man. The data provides evidence that catecholamines may influence insulin sensitivity in adipocytes.